Hollow cellulose fibers in which the cellulose is regenerated from cuoxam solutions are known for example from DE-A-23 28 853.
DE-C-29 06 576 teaches a method for spinning hollow fibers from regenerated cellulose for semipermeable membranes by extruding a cellulose-cuoxam solution through the annular slit of a hollow-fiber spinneret into an aqueous soda lye and extruding a cavity-forming fluid through the internal bore of the hollow-fiber spinneret and by conventional aftertreatment. Locating the hollow-fiber spinneret in the bottom of the coagulation tank is less favored because of technical problems in sealing and beginning spinning.
In order to avoid the known problems that can arise in using cavity-forming fluids to produce hollow fibers, it has already been proposed to use gases to form the internal cavity.
Thus, EP-B-0 076 442 teaches a method for manufacturing a hollow fiber from regenerated copper ammonium cellulose with an axially disposed cylindrical bore extending over the length of the fiber. The bore is filled exclusively with gas and contains no contaminants. EP-B-0 teaches a method with the following steps.
1) Extruding a spinning solution of copper ammonium cellulose through an annular opening, and forming a fiber extrudate with a bore, while gas is blown simultaneously into the fiber extrudate into the bore of the fiber through a blow tube located in the center of the annular opening;
2) Dropping the fibers in free fall in an air chamber and dipping them essentially perpendicularly to a depth of 2 to 20 mm, possibly also to a depth of up to 30 mm, below the surface of a coagulation bath only under the influence of a force directed downward and produced during free fall;
3) Guiding the fiber extrudate through the coagulating bath, producing a hollow fiber with an axially disposed cylindrical bore; and
4) Refining and drying the hollow fiber thus obtained.
The long air gap required for this purpose requires spinning solutions with a high viscosity. In addition, considerable difficulties arise in connection with the requirement of dipping the fiber in free fall up to 20 ml or possibly up to 30 ml deep in the coagulating bath. Dry elongation of such hollow fibers is approximately 40% and wet elongation is 70%, as is usual for conventionally spun hollow fibers as well.
Since the hollow fibers are produced from pure cellulose, the biocompatibility properties are much worse than for membranes that have been slightly modified for example. In addition, since materials that could be termed contaminating internal fluids under normal circumstances must not be present on the inside of the internal cavity, this rules out the possibility of improving biocompatibility by coating with suitable polymers usually ranked as contaminants. Substances that react with cellulose are likewise not provided according to this document.
DD-A-261 041 discloses a capillary hollow membrane made of regenerated cellulose (viscose) for liquid-phase permeation, with the internal cavity being formed by a gas or a liquid. Conventional viscoses with a high tendency to coagulate and the use of mildly coagulating precipitation baths characterizes the production of such hollow capillary membranes.
EP-A-0 135 593 teaches a hollow fiber for dialysis made of cuproammonium cellulose, which has a skin on the outside and no pores whatsoever on the inner surface. Elongation of such hollow fibers occurs in the range from +1.0 to -5.0%.
EP-B-0 175 948 describes the manufacture of nonstretched hollow fibers for dialysis by coagulating a cuproammonium cellulose solution with a cellulose concentration of 6.0 to 8.7 wt. % and a viscosity of 500-1300 poises (20.degree. C.), which has a film structure with a porosity of 15-25%, whose pores have a diameter of 25-40 .ANG., and whose ultrafiltration rate (UFR) is 3.0-5.5 ml/h.multidot.m.sup.2 .multidot.mmHg. The film structure must be essentially skin-free and essentially pore-free on the internal surface.
A major problem in dialysis is "biocompatibility," described below.
Tolerance of hemodialysis in patients is affected by various factors such as the physical and mental state of the patient, the sterile environment, and especially the dialyzer, with the biocompatibility of the hollow fiber in the dialysis module being an important factor. In addition, the surface properties of the polymer, the membrane structure, and the dialyzer design have a significant influence on biocompatibility in dialysis treatment.
The chemically different structures of the various polymers play an important role in biocompatibility, as for example in complement activation (C5aformation), hemolysis, and thrombogenesis.
In addition to the fact that dialysis membranes made of synthetic or natural polymers, when used in artificial kidneys, can very easily cause blood clotting which is largely prevented by suitable treatment with drugs, there is another effect that frequently occurs in dialysis membranes made of regenerated cellulose. Specificially when treating a kidney patient using a dialyzer with cellulose membranes a transient decrease in the number of leucocytes can occur at the beginning of dialysis treatment. This effect is known as leucopenia and must be at least largely suppressed or prevented by modifying the membrane.
Leucopenia in dialysis is most strongly evident 15 to 20 minutes after the start, when the neutrophils (in other words, the leucocytes that can be stained with neutral dyes or simultaneously with acid and basic dyes) can disappear almost completely. Then the number of leucocytes recovers within about 1 hour, back to nearly the initial value or even above the latter.
If a new dialyzer of the same kind is connected after the leucocytes recover, leucopenia again occurs to the same degree.
Cellulose membranes cause pronounced leucopenia. Although the clinical significance of leucopenia has not yet been scientifically explained, it is desirable to have a dialysis membrane for hemodialysis that does not show the effect of leucopenia but does not adversely affect the other highly desirable properties of dialysis membranes made of regenerated cellulose.
In hemodialysis using membranes made of regenerated cellulose, pronounced complement activation has been observed along with the leucopenia. The complement system within the blood serum is a complex plasma enzyme system composed of many components which works in different ways to defend against injury by invading foreign cells (bacteria, etc.). If antibodies against the invading organism are available, activation is possible in a complement-specific manner by the complex of antibodies with antigen structures of the foreign cells, otherwise complement activation takes place along an alternative path through special surface features of the foreign cells. The complement system is based on a number of plasma proteins. After activation, these proteins react specifically with one another in a certain sequence and finally a cell-damaging complex is formed which destroys the foreign cell.
Peptides are released from individual components, triggering inflammation phenomena and possibly also having undesired pathological consequences for the organism. It is assumed that activation in hemodialysis membranes made of regenerated cellulose takes place via the alternative path. These complement activations have been determined objectively by detection of complement fragments C3a and C5a.
Reference is made in this connection to the following papers: D. E. Chenoweth et al., Kidney International, Volume 24, Pages 764 et seq., 1983 and D. E. Chenoweth, Asaio-Journal, Volume 7, Pages 44 et seq., 1984.
Although the clinical significance of complement activation has not yet been explained, efforts are made to exclude it as much as possible in hemodialysis.